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Most addictive?

Clinical bottom line

Based on cessation rates with placebo, it can be argues that smoking is a harder addiction to stop than most others for which there is trail data with placebo.


Is it possible to tell which addiction is - well - strongest, worse, perhaps hardest to crack? Obviously every one of us will have some view on this, and it is likely that many of those views will have some degree of relevance or validity.

But can the evidence help? One way may be to compare across addictions what happens with placebo. To do this it is a requirement that we compare like with like.

Only systematic reviews or meta-analyses were used to look at this. Where several examined the same subject, the most recent and largest was chosen. For cessation, analyses that included predominantly short term outcomes were excluded. In general, articles with cessation rates after at least six months were chosen, but some also included a few studies with shorter duration (three months, for example). Those using randomised or quasi randomised trials were preferred; a few in areas with little evidence used controlled trials, generally but not exclusively randomised, and were included to provide some information.

Outcomes for cessation trials was quit rates - typically the percentage of participants abstinent according to an objective test of abstinence at six months or longer. Outcomes for relapse trials were more varied. Where possible we took the percentage of participants shown to be drug free by objective testing, but in some cases other less useful outcomes were reported and used, usually where there was little alternative information.

Another aim was to have reviews with at least two studies and at least 300 participants. This was not always possible, because it would have excluded many reviews on addictions other than smoking.


Figure 1 shows the comparison of cessation rates with placebo for nicotine, alcohol, cocaine, and opioids. There was a clear distinction between nicotine, with low cessation rates, and much higher cessation rates with cocaine and opioids. Alcohol was intermediate between these.

Figure 1: Cessation rates with placebo

Figure 2 shows the comparison of relapse rates with placebo for nicotine, alcohol, and opioids. There was no large difference between any of these, with relapse rates above 60%, and above 70% for nicotine.

Figure 2: Relapse rates with placebo


This review of reviews sought evidence of differences between addictions to different substances from responses to placebo using data from systematic reviews and meta-analyses of randomised trials reporting abstinence at six months or longer. The bulk of the data came from reviews of smoking cessation in over 127,000 participants, though reviews for treatments of other addictions covered a few thousand participants. Most of the reviews included had a preponderance of longer-term studies, with determination of abstinence using objective measures.

This strategy allows comparisons between placebo responses to different interventions in different addictions, and is designed to minimise issues of bias. The example of nicotine replacement therapy, with over 43,000 participants in trials of six months or longer, showed that vagaries of trial design made little difference to placebo response rates. Together, these approaches support the contention that cross-addiction comparisons may be justified.

It could be argues that a milder addiction would have higher cessation and lower relapse rates than an another addiction that was harder to give up. For nicotine and smoking, the cessation rate was much lower than other addictions (Figure 1), and relapse rate at least the same, if not higher (Figure 2).

The evidence we have suggests strongly that nicotine is the most difficult to give up. It does not support the hypothesis that addictions perceived to be mild are easy to give up. Either cessation rates do not adequately test the strength of an addiction, or the hypothesis is not true.

Not everyone is likely to agree with the hypothesis. There are other factors that could influence how people view the severity of an addiction, e.g. how rapidly it impairs health, whether the substance is legal, how much it alters behaviour (particularly antisocial behaviour), or the amount an individual consumes. Despite considerable searching, no study or other article could be found that addressed this question in any other way. Let us know if there's something obvious we have missed.